We propose to purchase a high-resolution micro-computed tomography (microCT) system for in vivo imaging of small animals (mouse, rat). The VivaCT 40 system (Scanco Medical) has a maximal spatial resolution of 10 [unreadable]m, making it appropriate for imaging trabecular bone microstructure, cortical thickness and vascular calcification in mice. MicroCT has become the standard for quantitative ex vivo assessment of bone morphology (especially of trabecular bone) in skeletal studies in mice. With in vivo microCT we will extend the benefits of microCT to longitudinal assessment. We have identified a major and minor user group of 12 investigators that represent six departments (Anatomy & Neurobiology, Biology, Medicine, Molecular Biology & Pharmacology, Orthopaedic Surgery, Pathology). The instrument will immediately benefit projects that are funded by 14 NIH grants from five Institutes (NIAMS, NCI, NICHD, NIDDK, NHLBI). Major uses include: assessing skeletal phenotypes in 1500 mice from recombinant and advanced intercross inbred strains used to map genes that regulate diabetes, obesity and bone properties; assessing skeletal responses to mechanical loading in osteoporotic mice and after damaging fatigue loading; assessing skeletal responses to loading and unloading in mice with osteoblast-specific deletion of the gap junction protein connexin43; monitoring the progression of vascular calcification in the aorta of mice on high fat diets and with manipulation of genes regulating the pro-osteogenic BMP2-Msx2-Wnt signaling cascade. The instrument will facilitate statistically powerful, longitudinal (repeated measures) study designs to monitor skeletal changes that are currently impossible to perform, except with low resolution methods such as DXA. In addition, by reducing the need for multiple groups for each timepoint, in vivo scanning will create more efficient utilization of existing human and animal resources across multiple projects. Finally, acquisition of the in vivo microCT instrumentation grant will contribute to the long-term goal of developing a Center for Musculoskeletal Research at Washington University. Relevance: Support of an in vivo microCT scanner will benefit ongoing research studies aimed at understanding the genes that regulate diseases such as diabetes and osteoporosis, as well as understanding how vascular calcification progresses in the context of diabetes. It will also benefit studies aimed at understanding how the skeleton responds to mechanical forces, which will in turn will contribute to discovery of strategies to enhance bone density and strength in osteoporosis. [unreadable] [unreadable] [unreadable]